Glucose Tolerance Index Research Articles

Reduced glucose effectiveness as a feature of glucose intolerance: Evidence in elderly Type-2 diabetic subjects

One of the factors determining glucose tolerance is glucose disappearance independent from the dynamic insulin (glucose effectiveness); the debate on its role in the development of Type-2 diabetes is still open. The aim of the present study was to evaluate insulin delivery, insulin sensitivity (SI), and glucose effectiveness (SG) in a group of elderly Type-2 diabetic patients (D, 4/6 F/M, age 67 +/- 2 years, 64 +/- 2 kg, BMI 23.8 +/- 0.5 kg/m2), compared to young controls (C, 4/6 F/M, 25 +/- 2 years, 72 +/- 4 kg, 23.7 +/- 1.1 kg/m2) and elderly controls (E, 2/4 F/M, 73 +/- 3 years, 63 +/- 4 kg, 23.1 +/- 0.5 kg/m2). We performed oral (OGTT) and intravenous (FSIGT) glucose tolerance tests. The OGTT showed that C and E were normotolerant, while D had a markedly reduced glucose tolerance. This was also confirmed in the FSIGT where the glucose tolerance index (KG) was 0.6 +/- 0.1% min-1 in D vs 1.8 +/- 0.2 in C and 1.5 +/- 0.2 in E (p < 0.0002). Total insulin area of D and the overall insulin delivery were not different from those of the control groups. The early phase area was instead significantly reduced (0.19 +/- 0.02 mU min/mL vs 0.61 +/- 0.06 of C and 0.46 +/- 0.06 of E, p < 0.001) given the reduction in the dynamic first-phase insulin delivery (0.86 +/- 0.17 min(microU/mL)/(mg/dL) vs 3.95 +/- 0.61 in C (p < 0.005) and 2.61 +/- 0.66 (p < 0.001) in E). SI of D was 3.4 +/- 0.4 10(-4) min-1/(microU/mL), not different from that of C (4.7 +/- 0.6) and E (3.5 +/- 0.2). This study showed a marked difference between SG of D and that of both control groups [0.010 +/- 0.001 min-1 vs 0.026 +/- 0.004 (p < 0.001) of C and 0.020 +/- 0.003 (p < 0.002) of E], mostly due to the zero-insulin component GEZI which was 0.006 +/- 0.001 in D vs 0.021 +/- 0.004 in C and 0.016 +/- 0.003 in E (p < 0.003). In the elderly groups, when taken together, SG exhibited a positive correlation with the area under insulin concentration during the early phase and with KG (r = 0.69, p = 0.0032 and r = 0.90, p = 0.0001, respectively), demonstrating the importance of the first-phase insulin delivery in modulating glucose effectiveness and glucose tolerance.

Relationships between IGF-I and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients.

To compare insulin-like growth factor-I (IGF-I) concentrations in obese and normal subjects, and evaluate the possible relationships between IGF-I concentrations and demographic, anthropometric, metabolic and hormonal variables in obese patients. 286 obese outpatients (OB, 234 female and 52 male; age 18-71 y, body mass index (BMI) > 27 kg/m2) were recruited. BMI, waist-to-hip ratio (WHR), serum basal and oral glucose tolerance test (OGTT)-stimulated glucose and insulin concentrations, IGF-I, basal growth hormone (GH), prolactin (PRL), androgens, thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), free fatty acids (FFA), triglycerides, total and high density lipoprotein (HDL)-cholesterol, 24h-urinary cortisol levels and blood pressure (BP) values were measured. IGF-I concentrations were also evaluated in a large population of 326 age-matched controls (controls, 228 women, 98 men; age 20-86 y, BMI < 25 kg/m2). IGF-I concentrations were lower in OB than in controls (age-adjusted mean: 21.6 vs 23.6 nmol/L, P < 0.03). However, individual IGF-I concentrations in OB were within the age-adjusted normal range. In both groups, IGF-I concentrations were gender-independent, and showed a simple negative correlation with age (r = -0.47). In OB, univariate analysis also shows that IGF-I concentrations were negatively correlated with BMI (r = -0.33), but not WHR, with both basal (r = -0.16) and OGTT-stimulated glucose levels (r = -0.17), as well as FFA levels (r = -0.19), and with both diastolic and systolic BP (both r = -0.17). In OB women, IGF-I concentrations positively correlated with PRL (r = 0.31), testosterone (r = 0.30), androstenedione (r = 0.30), and dehydroepiandrosterone-sulfate (DHEAS) concentrations (r = 0.41). No correlation was found with other variables. The multiple regression analysis showed that IGF-I concentrations were inversely and independently related to age and BMI only. In obesity, IGF-I concentrations are slightly reduced, but generally within the age-adjusted normal range. IGF-I concentrations in obesity show independent and negative relationships with age and BMI, but are not associated with fat distribution, insulin secretion, glucose tolerance, BP or risk indices for cardiovascular disease (CVD).

Insulin, branched-chain amino acids, and growth failure in uremia.

Insulin and branched-chain amino acid (BCAA) metabolism was studied in 14 adolescents with uremia on hemodialysis. Glucose tolerance was measured by intravenous glucose tolerance tests. Insulin sensitivity was measured by the euglycemia clamp technique. Insulin secretion during constant hyperglycemia was measured by the hyperglycemic clamp technique. Fasting plasma BCAA concentrations were compared with data from 8 adolescent controls, whereas insulin indices were compared with 8 young adults controls and with published normal data in adolescents. The patients could be further sub-divided into two groups with respect to their growth velocity standard deviation score (GVSDS). Group 1 consisted of 7 patients with GVSDS less than -2. This group demonstrated insulin resistance, glucose intolerance, and low insulin secretion. This group also had low plasma valine, leucine, and isoleucine concentrations compared with control values. Group 2 consisted of 7 patients with GVSDS more than -2. This group demonstrated insulin resistance, but normal glucose tolerance and normal insulin secretion. Plasma valine, leucine, and isoleucine concentrations in group 2 were not different from control values. Total plasma BCAA correlated with glucose tolerance index and with insulin secretion, but not with insulin sensitivity. Growth failure in uremia is associated with glucose intolerance, hypoinsulinemia, and low plasma BCAA concentrations. Impaired utilization of conventional energy sources leading to preferential oxidation of BCAA may contribute to reduced anabolism and growth failure in uremia.

Age-Related Reduction in Glucose Elimination Is Accompanied by Reduced Glucose Effectiveness and Increased Hepatic Insulin Extraction in Man1

This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (SG), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled i.v. glucose tolerance test was performed in 20 elderly (E, 10/10 male/female, all 63 yr old) and in 20 young subjects (Y, 10/10 male/female, all 27 yr old), who were similar in body mass index and 2-h blood glucose during oral glucose tolerance test. E exhibited impaired glucose elimination (i.v. tolerance index, 1.31 +/- 0.10 vs. 1.70 +/- 0.12% min-1; P = 0.019). First-phase insulin secretion and SI did not differ between the groups, whereas E had lower glucose sensitivity of second-phase insulin secretion (0.40 +/- 0.07 vs. 0.70 +/- 0.08 (pmol/L)min-2/(mmol/L), P = 0.026), lower SG, 0.017 +/- 0.002 vs. 0.025 +/- 0.002 min-1, P = 0.004), and higher HE (81.3 +/- 2.4 vs. 73.2 +/- 2.1%, P = 0.013). Across both groups, SG correlated positively with glucose tolerance index (r = 0.58, P < 0.001) and negatively with HE (r = -0.54, P < 0.001). Plasma leptin and glucagon did not change by age, whereas plasma pancreatic polypeptide (PP) was higher in E (122 +/- 18 vs. 66 +/- 6 pg/mL, P = 0.004). PP did not, however, correlate to any other parameter. We conclude that E subjects with normal oral glucose tolerance have reduced SG, impaired second-phase insulin secretion, and increased HE, whereas SI and first-phase insulin secretion seem normal. SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.

Effects of neutering on bodyweight, metabolic rate and glucose tolerance of domestic cats

Few controlled studies have been made of the possible mechanisms and physiological consequences of weight gain after cats have been neutered. In this study, six male and six female cats were gonadectomised and compared with five entire male and six entire female cats, before they were neutered and one and three months later. The neutered males gained significantly more weight (mean [SEM] per cent) than the entire males (30.2 [5·2] v 11·8 [2·3]) and the entire females gained 40·0 (7·3) v 16·1 (3·3) per cent, (P<0·05). The castrated males gained more weight as fat than the sexually intact males (22·0 [3·3] v 8·8 [4S] per cent, P<0·05). There was a significant increase (P<0·05) in daily food intake after neutering. Spayed females underwent a significant decrease in fasting metabolic rate (83·7 [5·5] v 67·2 [23] kcal/kg bodyweight 0·'75/day P<0·05). Gonadectomy had minimal effects on serum thyroid hormone concentrations, the resting or fasting metabolic rates in males, or on indices of glucose tolerance.

Quantification of the effects of troglitazone on insulin sensitivity and β-cell function in Watanabe heritable hyperlipidemic rabbits: A minimal model analysis

Troglitazone is a newly developed antidiabetic drug that has been shown to improve insulin resistance and hyperinsulinemia both in diabetic animal models and in patients with non—insulin-dependent diabetes mellitus. The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of familial hypercholesterolemia, is characterized by hyperinsulinemia, which reflects insulin resistance. In this study to determine the effects of troglitazone on glucose and insulin metabolism in WHHL rabbits, we quantified the rate of glucose utilization (glucose tolerance index [Kg]), sensitivity of first-phase posthepatic insulin secretion to glucose (Φ 1), sensitivity of second-phase posthepatic insulin secretion to glucose (Φ 2), insulin sensitivity to glucose disposal ([S i] inversely related to insulin resistance), insulin-independent glucose disposal (glucose effectiveness [S g]), and rate of insulin clearance (K i) by incorporating our previously reported two-compartment model of a glucose/insulin system with the glucose disappearance model of Bergman. Galvin insulin sensitivity (GIS) was also computed for comparison with Bergman S i. When troglitazone was administered as a food admixture (24 mg/d per animal) for 6 months, it did not significantly affect β-cell function as measured by Φ 2, glucose tolerance as measured by K g or S g, but increased both S i and K i and reduced Φ 1, leading to a decreased plasma insulin response during the intravenous glucose tolerance test (IVGTT). S i was strongly and significantly correlated with GIS. These data indicate that in WHHL rabbits, troglitazone improves insulin sensitivity and posthepatic insulin clearance without affecting β-cell function or glucose tolerance.

Influence of moderate physical exercise on insulin-mediated and non—insulin-mediated glucose uptake in healthy subjects

To establish the relative importance of insulin sensitivity and glucose effectiveness during exercise using Bergman's minimal model, 12 nontrained healthy subjects were studied at rest and during 95 minutes of moderate exercise (50% maximum oxygen consumption [V o 2max]). Each subject underwent two frequently sampled intravenous glucose tolerance tests (FSIGTs) for 90 minutes, at rest (FSIGTr) and during exercise (FSIGTe). Plasma glucose, insulin, and C-peptide were determined. Insulin sensitivity (S I), glucose effectiveness at basal insulin (S G), insulin action [X(t)], and first-phase (Φ 1) and second-phase (Φ 2) β-cell responsiveness to glucose were estimated using both minimal models of glucose disposal (MMg) and insulin kinetics (MMi). Glucose effectiveness at zero insulin (GEZI), glucose tolerance index (K G), and the area under the insulin curve (AUC 0–90) were also calculated. Intravenous glucose tolerance improved significantly during physical exercise. During exercise, S 1 (FSIGTr v FSIGTe: 8.5 ± 1.0 v 25.5 ± 7.2 × 10 −5 · min −1 [pmol · L −1] −1, P < .01), S G (0.195 ± 0.03 v 0.283 ± 0.03 × 10 −1 · min −1, P < .05), and GEZI (0.190 ± 0.03 v 0.269 ± 0.04 × 10 −1 · min −1, P < .05) increased; however, no changes in Φ 1 and Φ 2 were found. Despite a significant decrease in the insulin response to glucose (AUC 0–90, 21,000 ± 2,008 v 14,340 ± 2,596 pmol · L −1 · min, P < .01), insulin action [X(t)] was significantly higher during the FSIGTe. These results show that physical exercise improves mainly insulin sensitivity, and to a lesser degree, glucose effectiveness. During exercise, the insulin response to glucose was lower than at rest, but β-cell responsiveness to glucose did not change.

Impaired glucose tolerance in hypertension is associated with impaired insulin release independently of changes in insulin sensitivity

To assess the contribution of insulin release and glucose disposal by insulin-dependent and insulin-independent mechanisms to overall glucose tolerance in hypertension. Minimal model analysis of insulin and glucose data from frequently sampled intravenous glucose-tolerance tests from 21 non-diabetic, newly diagnosed hypertensives, and from 21 age- and weight-matched normotensive controls, was performed to obtain indices of glucose tolerance, beta-cell function and insulin sensitivity. Intravenous glucose tolerance (defined as the glucose disappearance rate constant) was significantly correlated with the minimal model parameters for insulin sensitivity, glucose effectiveness or insulin-independent glucose uptake, and first- and second-phase beta-cell responsiveness (phi 1 and phi 2). First-phase insulin release, expressed either as the area under the insulin-time curve between 0 and 10 min or as the ratio of that area to total insulin area was also correlated with glucose tolerance. Despite similar basal insulin and glucose concentrations, glucose tolerance was clearly diminished among the hypertensives. This could not be accounted for by insulin resistance or by changes in insulin-independent glucose uptake. Insulin release was diminished, as evidenced by the lower phi 2 among the hypertensives. phi 2 was inversely correlated with systolic (r = -0.44, P < 0.003) and diastolic (r = -0.42, P < 0.006) blood pressures. These differences were independent of body weight. Hypertensives also exhibited a lower fractional clearance rate for insulin. Impaired insulin release might contribute to the glucose intolerance associated with hypertension, and this can occur in the absence of insulin resistance, which is not present in all subjects with essential hypertension.

Day-long glucose, insulin, and fructose responses of hyperinsulinemic and nonhyperinsulinemic men adapted to diets containing either fructose or high-amylose cornstarch

Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed a typical American diet containing 20% of calories either as fructose or as high-amylose cornstarch for 5 wk in a crossover design to determine their effects on indices of glucose tolerance. Blood glucose, insulin, and fructose were determined before and 30, 60, 90, 120 and 180 min after breakfast, lunch, and dinner. Glucose responses were significantly lower 60 and 120 min and the insulin response lower 60 min after the meals containing fructose. Hyperinsulinemic men showed a tendency toward decreased insulin sensitivity after consuming fructose on the basis of an increased insulin-to-glucose ratio and decreased insulin binding to erythrocytes. These results generally show a beneficial effect of fructose on glucose tolerance; however, recommendations for including large amounts of fructose in the diet should also be based on a complete evaluation of the effect on other metabolic risk factors.

Early post-natal growth of large-for-dates babies of non-diabetic mothers is influenced by maternal glucose metabolism

Growth of weight, length, head circumference and skinfold thickness (subscapular and triceps) from birth to 6 months in 53 large-for-dates (LFD) Chinese babies weighing > 4.0 kg at term and born to non-diabetic mothers was investigated and correlated with biochemical indices of maternal glucose tolerance at birth: glycosylated haemoglobin (HbA 1), serum corrected fructosamine and the area under the oral glucose (50 g) tolerance (OGTT) curve. Growth in all physical dimensions, especially weight, showed a downward shift towards a reference mean. These changes in relative size were caused by slower growth velocities. None of the mothers had abnormally high concentrations of HbA, or fructosamine nor an abnormal OGTT. However, weight velocities did show small but significant correlations with fructosamine ( r = - 0.42), and OGTT area units ( r = 0.39) but not with HbA 1. For some macrosomic babies born to apparently normal mothers, birth is seen to interrupt a process operating in prenatal life that accelerates growth. Covert abnormalities of maternal glucose homeostasis could explain this. Abnormal glucose tolerance during pregnancy might therefore be viewed as a continuum extending from (i) its maximum expression, the frankly diabetic state, through (ii) gestational diabetes to (iii) the mother who has no biochemically evident abnormality of glucose homeostasis but who has sufficient alteration to modify fetal growth. Post-natal growth of LFD babies is additional information which, when taken along with other markers of maternal glucose tolerance, might help to identify the mother at later perinatal risk.

Effects of sugars on Indices of glucose tolerance in humans

Ten men and nine women were studied to determine whether replacement of utilizable complex carbohydrate by sugars (mono- and disaccharides) in a high-fiber, low-saturated fat diet would affect indices of glucose tolerance. Diets differed in that the 50% of calories derived from carbohydrate was either 35% complex and 15% sugars (low-sugar) or 15% complex and 35% sugars (high-sugar). Summation of glucose responses 30–180 min following an oral glucose tolerance test was significantly higher in men, but not women, after they consumed the high-sugar diet. Corresponding insulin responses were significantly higher in men consuming the high-sugar compared to the low-sugar diet. Insulin binding was significantly lower during the base line period and after the high-sugar diet compared to the low-sugar diet. Results indicate that sugars adversely affect indices of glucose tolerance when they replace complex carbohydrates even in a high-fiber, low-saturated fat diet.

Nutrient intake, adiposity, and diabetes.

To study the role of nutritional factors in the genesis of diabetes, estimations of blood sugar concentration, food intake, and adiposity (as body mass index; BMI) were carried out on three normal population samples--namely, 961 employees of Beecham Ltd, 1005 employees of the Greater London Council, and 1488 middle-aged male civil servants (Whitehall study). Blood sugar concentrations and indices of glucose tolerance correlated positively with the degree of adiposity but tended to be negatively correlated with total food energy intake and its component nutrients (total carbohydrate, sucrose, and fat). This inverse trend was largely accounted for by highly significant inverse correlations between food energy intake and adiposity, a relation found in both sexes and in all three population samples and which extended across the whole range of nutrient intake and BMI. These findings suggest that greater degrees of adiposity are associated with lower than average food energy intakes and hence lower total energy expenditures. The association of increased adiposity with low food energy consumption may indicate an underlying "low energy throughput" state, and it may be the mechanisms of this, as well as the obesity, that are responsible for disease.

Functional Alteration of Islet Cells After Jejunal or Ileal Resection in Dogs

Functional alteration of the islet cells was investigated in dogs after the resection of different parts of the small intestine. Three weeks after jejunal or ileal resection, when the dogs might still have been in a catabolic state, insulin and pancreatic glucagon release in response to intravenously infused glucose and arginine was reduced. Three months after jejunal resection, both intravenous glucose tolerance and insulinogenic index in the intravenous glucose tolerance test were significantly below the preoperative values (P less than 0.001, P less than 0.05), while pancreatic glucagon release in response to arginine infusion release. This functional alteration three months after jejunal resection was similar to that seen in diabetes mellitus. On the other hand, three months after ileal resection, insulin and pancreatic glucagon release was almost normal. We conclude that the jejunum plays a more important role in the enteroinsular system than the ileum and that prolonged interruption of this enteroinsular axis can cause insular disorder and what could hypothetically be called enterogenic chemical diabetes, in view of the altered glucose tolerance test and the alteration in insulin secretory response.

Relationships between maternal glucose intolerance and neonatal blood glucose

Blood glucose changes in 63 infants during the first three hours of life were related to indices of glucose tolerance of their mothers. Of the mothers, 34 had insulin-dependent diabetes, 16 had gestational diabetes, and 11 had minor abnormalities of glucose tolerance. The fasting blood glucose level of the mother and the umbilical cord blood glucose level were both proportional to the rate of glucose decline in the infant after birth which, in turn, was inversely related to the lowest glucose level attained within three hours. Hypoglycemia occurred in 77% of the infants of diabetic mothers, 25% of the infants of mothers with gestational diabetes, and one of 12 (8%) of infants of mothers with minor degrees of glucose intolerance. The blood glucose level at two hours during an oral glucose tolerance test in the mother can be used to predict the probability of her infant having neonatal hypoglycemia.

Immunoreactive insulin, glucose tolerance, and carbohydrate inducibility in types II, 3, IV, and V hyperlipoproteinemia.

The elevation of plasma glycerides by a high carbohydrate diet (carbohydrate induction) has been systematically correlated with glucose tolerance, insulin output and ponderal index in normals and in patients with different types of hyperlipoproteinemia. Carbohydrate inducibility (ΔTG) was similar in normals and patients with Type II hyperlipoproteinemia. Delta TG was nearly always much greater than normal in Type III, and was quite heterogeneous in type IV. The scatter in ΔTG values in Type V patients was extremely great. The basal triglyceride and ΔTG were positively correlated only in Type IV. Abnormal glucose tolerance was present in approximately one third of Types II and III, one half of Type IV and 80 per cent of Type V patients. Hyperinsulinemia was present in most Type V patients, while a majority of Type II and III patients had relatively normal insulin levels. Approximately one third each of the Type IV patients had low, normal, and abnormally high insulin levels. Increasing insulin and insulinogenic indices were correlated with increased ATG in the normal, but not in any of the patient groups. In the specific groups of hyperglyceridemic patients in this study, plasma insulin levels did not appear to be a primary determinant of the degree of carbohydrate induction.

The intravenous glucose tolerance test.

1. Two indices of glucose tolerance, the “total index” and the “increment index”, derived from an intravenous glucose tolerance test have been defined, and determined in, 20 normal and 15 diabetic subjects.2. The “total index” is based on the assumption that the rate of fall of blood glucose remains consistently proportional to the total blood glucose value. The “increment index” assumes that the rate remains proportional to the increment blood glucose value.3. The mean “total index” for 42 tests in 20 normal individuals was 1·37 and the mean “increment index” was 3·68.4. The mean “total index” for 21 tests in 15 mildly diabetic patients was 0·71 and the mean “increment index” was 1·83.5. With a constant loading dose of glucose both indices are reproducible in any one individual.6. Increasing the loading dose from 25 to 50 g. produced significant increases of the “total index” in 8 normal and 6 diabetic subjects. The “increment index” remained constant in both groups.7. As the “increment index” is reproducible in any one individual within a twofold variation in the dose of glucose injected, it is the preferable measure of glucose tolerance.